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- Title
Intracellular calcium concentration and activation of the Na+/H+ exchanger in essential hypertension.
- Authors
Poch, Esteban; Botey, Albert; Gaya, Joan; Darnell, Alejandro; Rivera, Francisca; Revert, Luis
- Abstract
To investigate the relationship between changes in intracellular calcium concentration ([Ca2+]i) and agonist-induced activation of the Na+/H+ exchanger in essential hypertension (EH), platelet [Ca2+]i and pHi were measured in 24 patients with EH (14 males) aged 48 ± 2 years and 23 matched normotensive controls (NT) (12 males) aged 45 ± 3 years. Measurements were done with spectrofluorimetry using the dyes Fura-2 for [Ca2+]i and BCECF for pHi. [Ca2+]i and pHi were measured in the resting condition and after stimulation in vitro with 0.1 U/ml human thrombin. The thrombin-induced rise in pHi was Na+ dependent and amiloride sensitive, indicating that it was mediated by the Na+/H+ exchanger. Unstimulated [Ca2+]i was higher in patients with EH than in NT (60 ± 3 vs. 48 ± 1 nmol/liter, P < 0.005), but there were no differences in resting pH, between both groups (7.16 ± 0.01 vs. 7.16 ± 0.008). In the presence of 1 mmol/liter external calcium (Ca2+o), thrombin-induced increment in [Ca2+]i was significantly greater in patients with EH than in NT (281 ± 21 vs. 206 ± 19; P < 0.05) as was the pH, increment (EH: 0.137 ± 0.01; NT: 0.095 ± 0.01; P < 0.05). Both agonist-induced increments in [Ca2+]i and in pH, were correlated with mean arterial pressure (MAP) only in the EH group (r = 0.58, P < 0.005 and r = 0.59, P < 0.005, respectively). The agonist-induced rise in pHi was positively correlated with the rise in [Ca2+]i both in the EH group (r = 0.65, P < 0.001) and in the NT (r = 0.55, P < 0.01). At higher doses of thrombin (2.5 U/ml), the enhanced increment in both platelet [Ca2+]i (EH: 732 ± 20; NT: 619 ± 15 nmol/liter, P < 0.05, N = 6) and in pHi (EH: 0.193 ± 0.001; NT: 0.150 ± 0.004 P < 0.005, N = 6) was also observed in patients with EH. In the absence of Ca2+o (chelated with EGTA), there were no significant differences between patients with EH and NT in thrombin-induced increases neither in [Ca2+]i (EH: 140 ± 18; NT: 121 ± 22 nmol/liter) nor in pHi (EH: 0.098 ± 0.01; NT: 0.079 ± 0.01). When the agonist-induced increase in [Ca2+]i was prevented with the Ca2+i chelator MAPTAM, no rise in pHi was observed in either group. In conclusion, in platelets challenged with thrombin, the agonist-induced activation of the Na+/H+ exchanger occurs in correlation with the increment in [Ca2+]i, and both are significantly increased in patients with EH only in the presence of Ca2+o. Furthermore, the magnitude of the agonist-induced changes in [Ca2+]i and in pHi showed a direct relationship with MAP in the EH group. The agonist-induced activation of the Na+/H+ exchanger requires a rise in [Ca2+]i both in patients with EH and in NT subjects.
- Subjects
CALCIUM; SODIUM; HYPERTENSION; THROMBIN; AMILORIDE; HYDROGEN; DIURETICS; PYRIDAZINES; BLOOD coagulation factors
- Publication
Kidney International, 1994, Vol 45, Issue 4, p1037
- ISSN
0085-2538
- Publication type
Article
- DOI
10.1038/ki.1994.140